This project describes the systematic development of antimycobacterial agents targeting the unique nature of the lipid components of the bacterial cell wall. The approaches are designed specifically to inhibit the activities of the b-keto-acyl-synthases which generate the long chain fatty acids. The strategy is based on the natural product lead compounds cerulinin and thiolactomycin both of which show activity against FAS I and II activities, and are active against M.avium and M. tuberculosis in vitro. Generation of synthetic analogues has lead to the identification of compound III-50 which shows activity both in vitro and in in vivo murine TB.